Many cellular events and processes are characterized by altered expression levels of one or more genes. Differences in gene expression correlate with many physiological processes such as cell cycle progression, cell differentiation and cell death. Changes in gene expression patterns also correlate with changes in disease or pharmacological state. For example, the lack of sufficient expression of functional tumor suppressor genes and/or the over expression of oncogene/protooncogenes could lead to tumorgenesis (Marshall, Cell, 64: 313-326 (1991); Weinberg, Science, 254: 1138-1146 (1991), incorporated herein by reference for all purposes). Thus, changes in the expression levels of particular genes (e.g. oncogenes or tumor suppressors) serve as signposts for different physiological, pharmacological and disease states.
Gene expression profiles produce a snapshot that reflects the biological status of the sample, but in many circumstances biological status will reflect more than one characteristic of the sample. For example, when comparing tumor samples from two patients, there will be changes that correlate with differences between the states of the tumors as well as changes that correlate with the different physiological states of the two patients. One aspect of the current invention is directed at identifying genes that are differentially expressed between two biological states as being further correlated with disease, physiological or pharmacological state.